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The flow and gradient patterns in aortic stenosis reflect the complex interaction of the valve and underlying comorbidities on the myocardium (Figure 1). In the presence of symptoms, we believe patients with paradoxical low-gradient (PLG) aortic stenosis have a syndrome akin to heart failure with preserved ejection fraction (HFpEF). As demonstrated by Dayan et al. (1), PLG aortic stenosis predominates in older patients, and has a higher prevalence of coronary artery disease, diabetes, and hypertension, as well as a tendency to female predisposition, all characteristics of HFpEF. Altered ventricular–arterial interaction is a key pathophysiological element of both entities (2). The increased afterload predisposes patients (particularly in women) to concentric myocardial remodeling and contractile dysfunction, thus explaining the lower gradients in PLG aortic stenosis and abnormal ventricular filling in HFpEF.

The Complex Interaction Between Aortic Stenosis and Underlying Medical Conditions on the Myocardium

There is evidence that the prognosis in both PLG aortic stenosis and HFpEF is largely driven by comorbidities. PLG aortic stenosis has features intermediate of those observed in concordant nonsevere and severe disease (3), challenging the notion that it is an advanced stage of severe aortic stenosis. Moreover, the majority of patients with PLG progressed in severity, with nearly one-half progressing to high-gradient severe aortic stenosis (4). Therefore, it is unlikely that the adverse cardiovascular prognosis associated with PLG aortic stenosis is solely driven by the degree of aortic stenosis but more likely associated with the underlying comorbidities. Similarly, in HFpEF, a high percentage of adverse outcomes are related to noncardiovascular comorbidities (5).

Dayan et al. (1) have demonstrated lower mortality in patients with PLG who had aortic valve replacement, regardless of flow status. This is encouraging. However, there was moderate-to-substantial heterogeneity of the pooled observational studies, and the benefits of surgery may not be generalizable. Although this meta-analysis has set the stage for future randomized controlled studies, careful patient selection will be crucial to examine the effects of aortic valve replacement in patients with PLG, the HFpEF of aortic stenosis.

Footnotes

Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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